JP 2002-513763 A (Patent Literature 1), JP 2002-154397 A (Patent Literature 2), JP 2002-521489 A (Patent Literature 3) disclose CpG oligonucleotide and the method of manufacturing them.
JP 2010-504750 A (Patent Literature 4) discloses that oligonucleotides, which have lipophilic substituted nucleotide analogues out of CpG motif, cause production of interferon-α (IFN-α).
Following Non Patent Literature 1 discloses that the S-form stereoisomer of CpG oligonucleotide trimer promotes MAPK signal. All of the disclosures of this reference are incorporated herein by reference.
Following Non Patent Literature 1 discloses PF-3512676 (Sequence No. 128), all parts of the sequence are phosphorothioated and S-form stereoisomer. Natural oligonucleic acid is readily reduced in vivo. Whereas, that are changed phosphoric acid ester bond of oligo nucleic acid (P—O bond) to phosphoric acid thioester bond (P—S bond), P—S modifications are difficult to be reduced in vivo.